Department of Cancer Biology and the Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02215, USA.
Department of Cancer Biology and the Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02215, USA.
Cell Chem Biol. 2021 Jul 15;28(7):1090-1100. doi: 10.1016/j.chembiol.2021.04.021. Epub 2021 Jun 4.
Deubiquitinating enzymes (DUBs) are a largely understudied and untapped resource in the toolkit of protein degradation functionalities. They comprise a large repertoire of enzymes that remove ubiquitin from substrates in a variety of cellular and pathophysiological contexts, and have enormous potential for research and clinical use. It is only within the last 5 years that potent, selective, and well-characterized small-molecule inhibitors of DUBs have been described. These compounds are now being used to study the biological roles of DUBs. Here, we describe downstream applications of small-molecule inhibitors for studying DUBs and provide a framework for future studies. We highlight recent examples of using these inhibitors to confirm and explore the role of these enzymes in both normal and pathological contexts. These studies represent the first steps in the burgeoning field of pharmacological and chemoproteomic studies of DUBs, which will be critical for the continued advancement of DUB field.
去泛素化酶（DUBs）在蛋白质降解功能的工具包中是一个很大程度上被低估和未被充分利用的资源。它们包含了大量的酶，能够在各种细胞和病理生理环境下从底物上去除泛素，具有巨大的研究和临床应用潜力。直到最近 5 年，才描述了强效、选择性和特征良好的 DUB 小分子抑制剂。这些化合物现在正被用于研究 DUB 的生物学作用。在这里，我们描述了小分子抑制剂在研究 DUB 方面的下游应用，并为未来的研究提供了一个框架。我们强调了最近利用这些抑制剂来确认和探索这些酶在正常和病理环境中的作用的例子。这些研究代表了 DUB 的药理学和化学蛋白质组学研究这一日益兴起的领域的第一步，这对于 DUB 领域的持续发展将是至关重要的。
